Cross aryl halides

The cross-coupling of aromatic and heteroaromatic rings has been carried out extensively[555]. Tin compounds of heterocycles such as oxazo-lines[556,557], thiophene[558,559], furans[558], pyridines[558], and seleno-phenes [560] can be coupled with aryl halides. The syntheses of the phenylo.xazoline 691[552], dithiophenopyridine 692[56l] and 3-(2-pyridyl)qui-noline 693[562] are typical examples. 

They have also developed a route to 2-allenylindole derivatives (98T13929). When prop-2-ynyl carbonates (76) are reacted with 73 in the presence of palladium catalyst, a cross-coupling reaction occurs to give 77a (46%) and 77b (45%). Under a pressurized carbon monoxide atmosphere (10 atm), the palladium-catalyzed reaction of 73 with 78 provides 79a (60%) and 79b (60%) (2000H2201). In a similar reaction, when the substrate is changed to aryl halides (80), 2-aryl-1-methoxyindoles such as 81a (70%) and 81b (60%) are prepared (97H2309). 

Closely related to the Heck reaction is the Sonogashira reaction i.e. the palladium-catalyzed cross-coupling of a vinyl or aryl halide 20 and a terminal alkyne 21 ... 

A co-solvent that is poorly miscible with ionic liquids but highly miscible with the products can be added in the separation step (after the reaction) to facilitate the product separation. The Pd-mediated FFeck coupling of aryl halides or benzoic anhydride with alkenes, for example, can be performed in [BMIM][PFg], the products being extracted with cyclohexane. In this case, water can also be used as an extraction solvent, to remove the salt by-products formed in the reaction [18]. From a practical point of view, the addition of a co-solvent can result in cross-contamination, and it has to be separated from the products in a supplementary step (distillation). More interestingly, unreacted organic reactants themselves (if they have nonpolar character) can be recycled to the separation step and can be used as the extractant co-solvent. 

Carbon-carbon bond formation reactions and the CH activation of methane are another example where NHC complexes have been used successfully in catalytic applications. Palladium-catalysed reactions include Heck-type reactions, especially the Mizoroki-Heck reaction itself [171-175], and various cross-coupling reactions [176-182]. They have also been found useful for related reactions like the Sonogashira coupling [183-185] or the Buchwald-Hartwig amination [186-189]. The reactions are similar concerning the first step of the catalytic cycle, the oxidative addition of aryl halides to palladium(O) species. This is facilitated by electron-donating substituents and therefore the development of highly active catalysts has focussed on NHC complexes. 

Radical-mediated silyldesulfonylation of various vinyl and (a-fluoro)vinyl sulfones 21 with (TMSlsSiH (Reaction 25) provide access to vinyl and (a-fluoro)vinyl silanes 22. These reactions presumably occur via a radical addition of (TMSlsSi radical followed by /)-scission with the ejection of PhS02 radical. Hydrogen abstraction from (TMSlsSiH by PhS02 radical completes the cycle of these chain reactions. Such silyldesulfonylation provides a flexible alternative to the hydrosilylation of alkynes with (TMSlsSiH (see below). On oxidative treatment with hydrogen peroxide in basic aqueous solution, compound 22 undergoes Pd-catalyzed cross-couplings with aryl halides. 

Chromans have been obtained by the Pd-catalysed intramolecular cross coupling reaction involving aryl halides containing an ortto-hydroxyalkyl substituent <96JA10333>. 

Scheme 28 Domino iron catalysis for cross-coupling of alkyl and aryl halides [90]...

The utility of the stepwise, double-coupling procedure is demonstrated in the parallel synthesis of Tamoxifen derivatives on solid support [127] (Scheme 1-29). 1-Alkenylboronates thus obtained by a diboration-cross coupling sequence are further coupled with p-silyUodobenzene supported on polymer resin. Using this strategy, each position about the ethylene core is modified by the appropriate choice of alkyne, aryl halide, and cleavage conditions for the synthesis of a library of Tamoxifen derivatives. 

Nickel(II) salts are able to catalyze the coupling of Grignard reagents with alkenyl and aryl halides. A soluble 6 -phosphine complex, Ni(dppe)2Cl2, is a particularly effective catalyst.266 The main distinction between this reaction and Pd-catalyzed cross... 

The generated palladium chlorides possessing phosphinous acid ligands were found to be remarkably active and efficient catalysts in the presence of bases for a variety of cross-coupling reactions of aryl halides with aiylboronic... 

This chemistry has been extended to terminal alkynes by first carrying out the cross-coupling of the alkyne and aryl halide using catalytic amounts of Pd and Cu salts and then employing catalytic amounts of Cul to affect the cyclization (Scheme 5).6... 

Transition metal-catalyzed transformations are of major importance in synthetic organic chemistry [1], This reflects also the increasing number of domino processes starting with such a reaction. In particular, Pd-catalyzed domino transformations have seen an astounding development over the past years with the Heck reaction [2] - the Pd-catalyzed transformation of aryl halides or triflates as well as of alkenyl halides or triflates with alkenes or alkynes - being used most often. This has been combined with another Heck reaction or a cross-coupling reaction [3] such as Suzuki, Stille, and Sonogashira reactions. Moreover, several examples have been published with a Tsuji-Trost reaction [lb, 4], a carbonylation, a pericyclic or an aldol reaction as the second step. 

The scope of Suzuki-Miyaura reactions is extremely broad, covering practically all types of organic residues. The cross-coupling of arylboronic acids with aryl halides or triflates is the most... 

Intramolecularly coordinated A1 and In compounds (e.g., (75), (76)) transfer the Me group in cross-coupling reactions with various aryl halides, including chlorides, catalyzed by Pd and Ni complexes.16 262 265 Monoorganobismuth compounds are reactive in cross-coupling reactions only if they contain an intramolecularly coordinating residue (77),266 267... 

The application of bases other than fluoride for activation of organosilicon compounds to crosscoupling is documented. NaOH can replace fluoride in the cross-coupling of aryl and alkenyldichloroalkylsilanes with aryl halides, including chlorides. Apart from providing milder reaction conditions, the reaction in the presence of NaOH is applicable to a wider range of substrates ((85) and (86)).294... 

Complexes ligated by alkylphosphines had been used rarely as catalysts in cross-coupling chemistry, but several studies suggested that they could catalyze the amination of aryl halides with higher selectivity and activity than catalysts of arylphosphines. Steric hindrance promotes reductive elimination at the expense of /3-hydrogen elimination.54 Therefore, reactions of primary amines and, in... 

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